Daratumumab Study in Advanced Multiple Myeloma

• Register: EUCTR
• Last refreshed on: 17 July 2017
• Main ID: EUCTR2013-000752-18-ES
• Date of registration: 08/08/2013
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public title: Daratumumab Study in Advanced Multiple Myeloma
• Scientific title: An Open-label, Multicenter, Phase 2 Trial Investigating the Efficacy and Safety of Daratumumab in Subjects With Multiple Myeloma Who Have Received at Least 3 Prior Lines of Therapy (Including a Proteasome Inhibitor and IMiD) or are Double Refractory to a Proteasome Inhibitor and an IMiD
• Date of first enrolment: 17/10/2013
• Target sample size: 110
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000752-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, Spain, United States

Contacts

• Name: Clinical Registry group
• Affiliation: Janssen-Cilag International N.V.

• Name: Clinical Registry group
• Affiliation: Janssen-Cilag International N.V.

Key inclusion & exclusion criteria

Inclusion criteria:
Principal Inclusion Criteria in Lay Language (for a complete list of
inclusion criteria refer to the protocol):

- Documented multiple myeloma according to protocol-defined criteria
- Evidence of disease progression based on International Myeloma Working Group criteria
- Evidence of response to at least 1 prior treatment regimen and received an alkylating agent either alone or in combination with other myeloma treatments - Received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an
immunomodulatory drug (IMiD) in any order during the course of treatment or patients whose disease is double refractory to a PI and an IMiD - Eastern Cooperative Oncology Group performance status score of 0, 1, or 2 - Agrees to protocol-defined use of effective contraception
- A woman of childbearing potential must have a negative serum or urine pregnancy test at screening
- Laboratory values and electrocardiogram within protocol-defined parameters at screening
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 83
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 27

Exclusion criteria:
Principal Exclusion Criteria in Lay Language (for a complete list of
exclusion criteria refer to the protocol):

- Received daratumumab or other anti-CD38 therapies previously - Received anti-myeloma treatment within 2 weeks before Cycle 1, Day 1
- Nonsecretory multiple myeloma - Previously received an allogenic stem cell transplant or has received an autologous stem cell transplantation within 12 weeks before Cycle 1, Day 1
- Received a cumulative dose of corticosteroids more than the equivalent of >=140 mg of prednisone within the 2?week period before Cycle 1, Day 1
- History of malignancy (other than multiple myeloma) within 5
years before Cycle 1, Day 1 (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence)
- Exhibiting clinical signs of meningeal involvement of multiple myeloma
- Known chronic obstructive pulmonary disease, persistent asthma, or a history of asthma within 5 years - Seropositive for human immunodeficiency virus, hepatitis B or antibodies to hepatitis B surface and core antigens, or hepatitis C
- Any concurrent medical condition or disease that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study
- Clinically significant cardiac disease, including myocardial infarction within 1 year before Cycle 1, Day 1, unstable or uncontrolled disease/condition related to or affecting cardiac function, cardiac arrhythmia, or clinically significant
electrocardiogram abnormalities - Known allergies, hypersensitivity, or intolerance to monoclonal antibodies
or human proteins or their excipients, or known sensitivity to mammalian-derived products
- Has plasma cell leukemia, Waldenstrom?s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein, and skin changes), or amyloidosis
- Woman who is pregnant or breast-feeding or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study drug
- Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before Cycle 1, Day 1 (except for investigational
anti-myeloma agents, which cannot be taken within 2 weeks prior to Cycle 1, Day 1, as described in the protocol)
- Had major surgery within 2 weeks before Cycle 1, Day 1, or will not have fully recovered from surgery, or has surgery planned during the time the patient is expected to participate in the study or within 2 weeks after the last dose of study drug administration (Note: patients with planned surgical procedures to
be conducted under local anesthesia may participate)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Multiple myeloma
MedDRA version: 16.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Daratumumab
Product Code: HuMax-CD38
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Daratumumab
CAS Number: 945721-28-8
Current Sponsor code: JNJ-54767414 (Daratumumab)
Other descriptive name: HUMAX-CD38
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Secondary Objective: ? To assess the safety and tolerability of daratumumab.
? To assess the pharmacokinetics of Phase 2 drug product and Phase 3 drug product.
? To evaluate duration of and time to response to daratumumab.
? To determine the clinical benefit (CR+PR+MR) rate following treatment with daratumumab.
? To evaluate clinical outcomes including time to disease progression (TTP), PFS, and OS.
? To assess the pharmacokinetics, pharmacodynamics, and generation of antibodies to daratumumab (immunogenicity).
? To explore biomarkers predictive of response to daratumumab.

Timepoint(s) of evaluation of this end point: Up to 6 months after the last participant is enrolled in the study

Main Objective: The primary objective is to determine the efficacy of 2 treatment regimens of daratumumab, as measured by the overall response rate (ORR) (complete response [CR] + partial response [PR]),
in subjects with multiple myeloma who have received at least 3 prior lines of therapy including a PI and an IMiD or whose disease is double refractory to both a PI and an IMiD.

Primary end point(s): Overall response rate

Secondary Outcome(s)

Secondary end point(s): For a full list of secondary end point refer to protocol:-

1. Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT)
2. Duration of response
3. Overall survival
4. Clinical benefit rate
5. Time to response

Timepoint(s) of evaluation of this end point: For a full list of timepoint(s) of evaluation of secondary endpoint refer to protocol:-

1. Up to 30 days after the last dose of study medication
2. From the date of initial documentation of a response (complete
or partial response) to the date of first documented evidence
of progressive disease as defined by International Myeloma
Working Group criteria
3. From the date of the first dose of daratumumab administered
to the date of the participant?s death
4. Up to 8 weeks after the last dose of daratumumab
administered
5. From the first dose of daratumumab administered and the first
efficacy evaluation that the participant has met all criteria for
complete or partial response

Secondary ID(s)

54767414MMY2002

2013-000752-18-BE

Source(s) of Monetary Support

Janssen Research & Development, LLC